Process Development and Pilot-Scale Synthesis of Cefotetan

Abstract

Strategies that were adopted during the process development of Cefotetan in order to achieve a cost-effective commercial-scale synthesis are described herein. These included replacement of the trifluoroacetic acid used for cleavage of the benzhydryl ester and the development of an alternative synthetic route. This work led to improvement of both the impurity profile and the yield of the process. The pilot-scale synthesis of Cefotetan is described in detail in the Experimental Section. The scaled-up process has been successfully used for the commercial manufacture of Cefotetan since 1983.

Survey of Solvent Usage in Papers Published inOrganic Process Research&Development1997–2012

“…4,8 In the publication data set, we only found one paper which used benzene as solvent, but this process was run on more than 400 kg scale. 12 We also found a batch process using chloroform reported in OPRD at more than 1500 kg scale. 13 Full details of the survey with usage on each individual year can be found in the Supporting Information.…”

“…Pfizer has not transferred a commercial process which used a chlorinated solvent to its manufacturing division in the last eight years and has reduced chloroform usage in its medicinal chemistry group by 99% (usage by the process chemistry group was stopped decades ago) . In spite of these successes it is clear from Figure that the global industry as a whole is not making any significant progress and that materials such as chloroform, diethyl ether, n -hexane, diisopropyl ether, and 1,2-dichloroethane are still being selected for use when alternatives are readily available. , In the publication data set, we only found one paper which used benzene as solvent, but this process was run on more than 400 kg scale . We also found a batch process using chloroform reported in OPRD at more than 1500 kg scale .…”

Nano-Conversion of Ineffective Cephalosporins into Potent One against Resistant Clinical Uro-Pathogens via Gold Nanoparticles

“…SPR band peaks for CT-AuNPs and CX-AuNPS were observed at 542 nm and 522 nm, respectively ( Figure 2 ). Additional peaks at 254 nm [ 26 ] and 290 nm [ 27 ] were also observed during spectrophotometric scanning that corresponds to CT and CX, respectively, which suggested the successful loading of CT and CX onto AuNPs ( Figure 2 ). In accordance, similar dual peaks have been reported by several recent investigations on antibiotic-mediated AuNPs synthesis [ 11 , 12 , 13 , 14 , 15 ].…”

“…After AuNPs synthesis by CT and CX, the 3 mL reaction mixtures were centrifuged for 30 min at 30,000× g and the supernatants were cautiously taken into a separate falcon tube. The concentration of unbound CT and CX were estimated in the supernatant at 254 nm [ 26 ] and 290 nm [ 27 ], respectively by using their pre-determined calibration curve. Further, the loading efficiency % for each AuNPs sample was estimated by applying the following formula [ 28 ]: % of loading efficiency = [(Y − Z)/Y] × 100 where, Y is the initial concentration of CT or CX used for the AuNPs synthesis, and Z is the remaining (unbound) concentration of CT or CX in the supernatant.…”

Design, Synthesis, and Evaluation of Cephamycin-Based Antisporulation Agents targeting Clostridioides difficile

“…. 13 To a solution of 7-MAC (1.32 g, 2.50 mmol) in anhydrous CH 2 Cl 2 (12 mL) under N 2 at −20 °C (NaCl/ice) was added pyridine (0.628 mL, 7.76 mmol, 3.1 equiv), and the resulting solution was stirred for 5 min. Bromoacetyl bromide (0.589 mL, 6.76 mmol, 2.7 equiv) was then added dropwise to the solution over 10 min.…”